A recent review article published in the November 2016 issue of The American Journal of Psychiatry has claimed that the assumption of fear and anxiety being mediated in the brain by a single fear circuit is wrong and that it delayed the advancements in discovering the right treatments for anxiety problems.

The authors, Daniel Pine, M.D. from the NIMH Emotion and Development Branch, and Joseph LeDoux, Ph.D. from New York University, argue that designing future anxiety research based on a “two-system” framework can actually improve treatment outcomes for anxiety disorders. Pine has been involved in brain imaging studies of anxiety disorders and LeDoux is well-known for discovering brain circuitry underlying threat processing.

The authors claim that subjective feeling states are mediated by different circuitry unlike defensive behaviors. Fear is mediated in the brain via higher order processing in the cortex while anxiety is mediated via the amygdala and related centers, mostly in the deeper parts of the brain. The amygdala, often called as the brain’s “fear center,” unconsciously senses and responds to imminent threats and adds to fear only indirectly. States like anxiety, on the other hand, arise from areas of the cortex coupled with higher-order thinking processes and language in people, only some of which occur in animals.

The authors commented that fear and anxiety are not products of circuitry that would control defensive behavior, so studies concerning defensive behavior among animals and may not be useful in discovering drugs that can help relieve fear and anxiety in humans. They also remarked that formulating such distinctions will be useful in designing better realistic translational studies.

Meanwhile these distinctions can also affect expectations for the discovery of certain specific anti-anxiety medications. The authors note that existing medications are blunt tools, and that if fear and anxiety are from cortical changes in cognition, memory and attention, some effects that counter anxiety may result from emotional numbing or impaired thought processing. To improve a treatment method, the disease mechanisms should be clearly understood, and existing treatments could be modified to function effectively, with the help of the two-system perspective.


LeDoux, J. E., & Pine, D. S. (2016). Using Neuroscience to help understand fear and anxiety: A Two-System framework. American Journal of Psychiatry, 173(11), 1083–1093. https://www.ncbi.nlm.nih.gov/pubmed/27609244. Accessed at 25 November 2016.